Davis declined to be a candidate for reelection in 1846, but instead resumed the practice of law and also engaged in agricultural pursuits.

Davis was opposed to secession, however, and supported the Constitutional Union Party ticket of John Bell and Edward Everett in the 1860 presidential election.

This convinced him to reenter politics, and he was elected to the U.S. Senate as a Union Democrat by the Kentucky General Assembly in a December 1861 special election to fill the vacancy caused by the expulsion of John C. Breckinridge for supporting the Confederacy.

At the time of his death he was chairman of the Committee on Private Land Claims (during the 42nd Congress).

Davis' home, called Woodhome, was afterward sold to George Edgar who used it for a military academy.